Обоснование. В патогенезе и развитии атопического дерматита (АтД) важную роль играют генетическая предрасположенность, двухфазный иммунный ответ, дисбаланс T1- и Т2-лимфоцитов, нарушение функции эпидермального барьера, участие триггерных факторов, различных антигенов. В последнее время активно изучаются генотипы, эндотипы заболевания, а также взаимосвязь генетических факторов, особенностей патогенеза и клинической картины АтД, которая определяет фенотип заболевания. Цель. Изучить клинические особенности различных фенотипов АтД. Материалы и методы. Проведено открытое проспективное исследование, в котором приняли участие 86 пациентов со среднетяжелым и тяжелым течением АтД, в том числе 25 детей в возрасте от 2 до 18 лет и 61 взрослый в возрасте от 19 до 54 лет. Пациенты наблюдались в отделении аллергологии и иммунопатологии кожи ФГБУ ГНЦ Институт иммунологии ФМБА России в период с 2012 по 2016 г. Период наблюдения за пациентами составил не менее 1 года. Критериями отбора данной группы послужили возможность сбора полноценного анамнеза, проведение оптимального аллергологического обследования, оценки тяжести течения заболевания и ответа на проводимую терапию, адекватность выполнения пациентами рекомендаций врача, включая соблюдение элиминационных мероприятий, диеты, рациональный уход за кожей, а также применение наружной терапии. Все 86 пациентов данной группы получали стандартную терапию в соответствии с современными российскими и международными клиническими рекомендациями. В течение периода наблюдения проводили оценку степени тяжести заболевания на основании индексов SCORAD и IGA, эффективности наружной терапии и частоты развития нежелательных явлений. Результаты. Установлены основные критерии для определения клинических фенотипов АтД по показателям тяжести течения: степень тяжести заболевания (на основании индексов SCORAD, IGA) частота и длительность обострений возраст дебюта заболевания вторичная инфекция кожи сопутствующие респираторные аллергические заболевания и сенсибилизация к различным группам аллергенов резистентность к терапии. Рецидивирующее течение АтД заболевания и резистентность к стандартной терапии топическими глюкокортикостероидами отмечались у 8 (32) детей и 20 (32,7) взрослых. Результаты углубленного обследования репрезентативной выборки пациентов позволили выделить несколько фенотипов АтД: изолированный неосложненный АтД - у 15 пациентов АтД, осложненный вторичной инфекцией и сенсибилизацией к бактериальным или грибковым аллергенам, - у 7 пациентов АтД, сопровождающийся сопутствующими респираторными аллергическими заболеваниями и сенсибилизацией к пищевым и ингаляционным аллергенам, - у 29 пациентов АтД крайне тяжелого течения, сопровождающийся вторичной инфекцией, респираторными аллергическими заболеваниями и поливалентной сенсибилизацией, резистентностью к терапии, - у 36 пациентов. Заключение. Выделение клинического фенотипа позволяет дифференцировать пациентов в зависимости от клинических характеристик и особенностей течения АтД, что может быть полезным для понимания этиопатогенеза заболевания у конкретного пациента и позволит разработать персонифицированные подходы к диагностике и лечению АтД.Genetic predisposition, twophase immune response, T1 and T2 lymphocytes dysbalance, epidermal barrier dysfunction, trigger factors, antigens play an important role in the atopic dermatitis pathogenesis. Recently, genotypes, phenotypes of the disease, as well as the relationship of genetic factors, pathogenesis and clinical features of AD, which determine the phenotype of the disease, are actively studied. The purpose of this research was to evaluate the clinical features of different AD phenotypes. Materials and methods. The research was conducted as an open prospective study. 86 patients suffered from moderate and severe AD, including 25 children aged 2 to 18 years and 61 adults aged 19 to 54 years were involved. Patients in the skin allergy and immunopathology department of The Institute of Immunology of the FMBA of Russia in the period from 2012 to 2016 were observed. The followup period was at least 1 year. The inclusion criteria of this group were the ability to collect a full anamnesis, the allergological examination, assessment of the severity of the disease and the response to the therapy, the adequacy of the fulfilment of the doctors recommendations by the patients, including compliance with elimination measures, diet, rational skin care, as well as the use of topical treatment. All patients received standard therapy according to Russian and international clinical guidelines. The severity of the disease was assessed on the basis of SCORAD and IGA scales, effectiveness of topical treatment and adverse events frequency. Results. The main criteria for determining of AD clinical phenotypes were established: severity of the disease (based on SCORAD, IGA) frequency and duration of exacerbations age of onset of the disease secondary skin infection concomitant respiratory allergic diseases and sensitization to different groups of allergens resistance to therapy. Recurrent course of AD and resistance to standard topical corticosteroids therapy were observed in 8 (32) children and in 20 (32.7) adults. The results of examination of representative sample of patients allowed to identify and characterize several AD phenotypes: isolated uncomplicated AD - in 15 of patients AD complicated by secondary infection and the presence of sensitization to bacterial or fungal allergens - in 7 of patients AD accompanied by the concomitant respiratory allergic diseases and the presence of sensitization to food and respiratory allergens - in 29 of patients extremely severe AD, accompanied by secondary infection, respiratory allergic diseases and polyvalent sensitization, resistance to therapy - in 36 of patients. Conclusion. Identification of the clinical phenotype allows to determine the patients on the grounds of the clinical characteristics and AD features, which can be useful for understanding the etiopathogenesis of the disease in a particular patient and can be the basis for development of personalized approaches to the diagnosis and treatment of AD.
BACKGROUND:Atopic dermatitis (AD) is a widespread chronic inflammatory skin disease, in the development of which complex genetic and immune mechanisms, environmental factors, allergens, are involved. An effective method of treating IgE-mediated allergic diseases is allergen-specific immunotherapy (ASIT), which affects all pathogenetically significant links of the allergic process. It is known that as a result of ASIT tissue sensitivity to an allergen, nonspecific tissue hyperreactivity and the intensity of allergic inflammation decrease, which testifies to the rearrangement of the cellular response from Th2 to Th1 with a corresponding change in the cytokine profile. Currently, dozens of scientific papers on the efficacy and safety of subcutaneous and sublingual ASIT in AD have been published; however, the question of the advisability of its appointment still remains unresolved. AIM:To investigate the ASIT with house dust mite (HDM) allergens efficacy in AD patients, considering the results of molecular allergy diagnosis. MATERIALS AND METHODS:The study was conducted as a prospective comparative open study, including 32 patients with AD (20 children and 12 adults), 90.6% were diagnosed with concomitant respiratory allergic diseases. Molecular allergodiagnostics was performed using microchip technology with purified natural or recombinant allergen components immobilized in the solid phase (Immuno-Solid phase Allergen Chip, ISAC) to quantify allergen-specific IgE (asIgE) against 112 allergen molecules from 51 allergen sources in one study (ImmunoCAP ISAC (Thermofisher, Phadia, Uppsala, Sweden). Patients were divided into two groups depending on the profile of molecular sensitization: with the presence or absence of asIgE to the major allergens ofD. farinaeand/orD. pteronyssinusDer p 1 (p 2) and/or Der f 1 (f 2). All patients passed three consecutive courses of subcutaneous ASIT with water-salted HDM allergens produced by I.I. Mechnikov Biomed (Russia) under an accelerated scheme for 3 years. To assess the severity of the disease, the SCORAD indices, the Investigators Global Assessment (IGA), and the dermatological quality of life index (DLQI) were used. RESULTS:Patients with sensitization to major allergens ofD. farinaeand/orD. pteronyssinusDer p 1 (f 1) and/or Der p 2 (f 2) more often achieved a significant improvement of AD symptoms according to the SCORAD index (OR 3.929, 95% CI: 0.879; 17.56), as well as they more often achieved IGA values of 1 or 0 after three courses of ASIT (OR 3.556, CI 95% 0.73017.324) and more often assessed the effectiveness of ASIT as excellent and good in comparison with patients without sensitization to these components. The median and interquartile range of the DLQI index before treatment in group 1 was 17 [14; 20] points, in group 2 14 [12; 18], after the 3rdcourse of ASIT: 6 [2; 10] and 8 [3; 10] points in groups 1 and 2, respectively. Adverse events were rare, their frequency did not significantly differ in both groups. CONCLUSION:ASIT with HDM allergens is an effective and safe method of treatment of AD patients. Determination of the molecular spectrum of sensitization to HDM allergens components allows to justify the indications and predict the effectiveness of ASIT.
Background. The clinical efficiency and safety of tacrolimus ointment 0,1%, accessible in the Russian market since 2011, in moderate and severe atopic dermatitis (AD) were investigated. The assessment was based on the data of tacrolimus using in routine clinical practice under the registered indication. Methods. There were 19 moderate and 11 severe AD patients under supervision. Treatment with tacrolimus ointment 0,1% was started with twice a day application. Duration of this treatment was from 1 to 4 weeks (18±4,2 days) up to skin clearance. When symptoms were reduced, the frequency of tacrolimus application was reduced as well to once a day daily, and than to twice a week. Generally, improvement was observed within one week of treatment. Clinical efficiency was assessed by SCORAD index and Investigators' Global Assessment (IGA). Results. Positive clinical effect of tacrolimus 0,1% ointment therapy was found in 90% of AD patients resulted in significant reduction of dryness, rushes, skin itch, SCORAD and IGA indexes. Conclusion. Tacrolimus 0,1% ointment is effective and safe for treatment of severe and moderate AD. It should be applied both as exacerbations treatment and as maintenance therapy in AD patients.
The article contains a description of the various groups of drugs for topical treatment of atopic dermatitis with an assessment of their effectiveness, as well as the influence on the mechanisms of the immune response.
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